Zeiad Rawah K H M, Ferren Edwin C, Young Denise D, De Lancy Shanelle J, Dedousis Demitrios, Schillaci Lori-Anne, Redline Raymond W, Saab Shahrazad T, Crespo Maricruz, Bhatti Tricia R, Ackermann Amanda M, Bedoyan Jirair K, Wood Jamie R
Division of Pediatric Endocrinology, Department of Pediatrics, University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital, Case Western University School of Medicine, Cleveland, OH, USA.
Department of Genetics and Genome Sciences and Center for Human Genetics, University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital, Case Western University School of Medicine, Cleveland, OH, USA.
J Endocr Soc. 2021 Jan 2;5(2):bvaa196. doi: 10.1210/jendso/bvaa196. eCollection 2021 Feb 1.
Aminoacyl-tRNA synthetases (ARSs) are crucial enzymes for protein translation. Mutations in genes encoding ARSs are associated with human disease. Tyrosyl-tRNA synthetase is encoded by which is ubiquitously expressed and implicated in an autosomal dominant form of Charcot-Marie-Tooth and autosomal recessive related multisystem disease. We report on a former 34-week gestational age male who presented at 2 months of age with failure to thrive (FTT) and cholestatic hepatitis. He was subsequently diagnosed with hyperinsulinemic hypoglycemia with a negative congenital hyperinsulinism gene panel and F-DOPA positron-emission tomography (PET) scan that did not demonstrate a focal lesion. Autopsy findings were notable for overall normal pancreatic islet size and morphology. Trio whole exome sequencing identified a novel homozygous variant of uncertain significance in (c.611A > C, p.Tyr204Cys) with each parent a carrier for the variant. Euglycemia was maintained with diazoxide (max dose, 18 mg/kg/day), and enteral dextrose via gastrostomy tube (G-Tube). During his prolonged hospitalization, the patient developed progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay. Such multisystem features have been previously reported in association with pathogenic mutations. Although hypoglycemia has been associated with pathogenic mutations, this report provides more conclusive data that a variant can cause hyperinsulinemic hypoglycemia. This case expands the allelic and clinical heterogeneity of -related disease. In addition, -related disease should be considered in the differential of hyperinsulinemic hypoglycemia associated with multisystem disease.
氨酰-tRNA合成酶（ARSs）是蛋白质翻译的关键酶。编码ARSs的基因突变与人类疾病相关。酪氨酰-tRNA合成酶由[基因名称未给出]编码，该基因广泛表达，并与常染色体显性遗传性夏科-马里-图斯病及常染色体隐性相关多系统疾病有关。我们报告了一名孕34周出生的男性，2个月大时出现生长发育迟缓（FTT）和胆汁淤积性肝炎。随后他被诊断为高胰岛素血症性低血糖，先天性高胰岛素血症基因检测结果为阴性，F-DOPA正电子发射断层扫描（PET）未显示局灶性病变。尸检结果显示胰岛大小和形态总体正常。三联体全外显子测序在[基因名称未给出]中发现了一个意义不明的新纯合变异（c.611A>C，p.Tyr204Cys），其父母均为该变异的携带者。通过二氮嗪（最大剂量，18mg/kg/天）和经胃造口管（G管）给予肠内葡萄糖维持血糖正常。在他长期住院期间，患者出现了进行性肝病、外分泌性胰腺功能不全、急性肾衰竭、反复感染、鱼鳞病、血液系统问题、肌张力减退和全面发育迟缓。此前已有报道称这些多系统特征与致病性[基因名称未给出]突变有关。虽然低血糖与致病性[基因名称未给出]突变有关，但本报告提供了更确凿的数据，表明[基因名称未给出]变异可导致高胰岛素血症性低血糖。该病例扩展了[基因名称未给出]相关疾病的等位基因和临床异质性。此外，在鉴别与多系统疾病相关的高胰岛素血症性低血糖时，应考虑[基因名称未给出]相关疾病。
